scholarly journals DNA methylation age analysis of rapamycin in common marmosets

GeroScience ◽  
2021 ◽  
Author(s):  
Steve Horvath ◽  
Joseph A. Zoller ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Ken Raj ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rhesus Macaques ◽  
Common Marmoset ◽  
Primate Species ◽  
Vervet Monkeys ◽  
Methylation Data ◽  
Common Marmosets ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

scholarly journals DNA methylation age analysis of rapamycin in common marmosets

2020 ◽  
Author(s):  
Steve Horvath ◽  
Joseph A. Zoller ◽  
Amin Haghani ◽  
Ake T. Lu ◽  
Ken Raj ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rhesus Macaques ◽  
Common Marmoset ◽  
Primate Species ◽  
Vervet Monkeys ◽  
Methylation Data ◽  
Common Marmosets ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Common

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

scholarly journals DEVELOPMENT OF EPIGENETIC MEASURES FOR GEROSCIENCE CLINICAL TRIALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S746-S746
Author(s):  
Morgan E Levine
Keyword(s):  
Dna Methylation ◽  
Clinical Trials ◽  
Surrogate Endpoints ◽  
Methylation Data ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Epigenetic Age ◽  
Human And Mouse ◽  
Promising Avenue

Abstract One of the major goals of the NIA is to oversee development of biomarkers of aging. In recent years, DNA methylation has emerged as a promising avenue from which to quantify biological age. We and others have shown that these measures track age across various tissues and cells, and further deviations between chronological and “epigenetic age” have been shown to confer risk for various aging outcomes. However, the usefulness of these measures will depend on both their modifiability and ability to capture known targetable hallmarks of aging. Using DNA methylation data from cell line experiments, we have recently generated epigenetic predictors of cellular senescence for both human and mouse that when assessed in vivo from bulk samples, show age-related increases and are associated with aging outcomes. In moving forward, measures such as these may serve as promising surrogate endpoints for assessing efficacy of senolytic drugs and/or other anti-aging therapeutics.

scholarly journals Epigenetic clock and methylation studies in vervet monkeys

2020 ◽  
Author(s):  
Anna J. Jasinska ◽  
Amin Haghani ◽  
Joseph A. Zoller ◽  
Caesar Z. Li ◽  
Adriana Arneson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Primate Species ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Vervet Monkeys ◽  
Maximum Lifespan ◽  
Primate Model ◽  
Tissue Samples ◽  
Relative Age ◽  
Biomarkers Of Aging

ABSTRACTDNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes hypermethylated with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED, and genes possessing the trimethylated H3K27 mark in their promoters.The epigenetic clocks are expected to be useful for age estimation of wild-born animals and anti-aging studies in vervets.

scholarly journals Epigenetic clock and methylation studies in vervet monkeys

GeroScience ◽  
2021 ◽  
Author(s):  
Anna J. Jasinska ◽  
Amin Haghani ◽  
Joseph A. Zoller ◽  
Caesar Z. Li ◽  
Adriana Arneson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Primate Species ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Vervet Monkeys ◽  
Maximum Lifespan ◽  
Primate Model ◽  
Tissue Samples ◽  
Relative Age ◽  
Biomarkers Of Aging

AbstractDNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.

scholarly journals GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology

2004 ◽  
Vol 85 (9) ◽  
pp. 2525-2533 ◽  
Author(s):  
James R. Jacob ◽  
Kuei-Chin Lin ◽  
Bud C. Tennant ◽  
Keith G. Mansfield
Keyword(s):  
Acute Hepatitis ◽  
New World ◽  
Antiviral Drug ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Primate Species ◽  
New World Primates ◽  
Common Marmosets ◽  
The Common ◽  
Human Primate

GB virus B (GBV-B) is a flavivirus that is related closely to hepatitis C virus (HCV) and induces an acute hepatitis when inoculated into several species of New World primates. Common marmosets (Callithrix jacchus) are a widely available, non-endangered primate species that is susceptible to GBV-B infection and develops a characteristic acute hepatitis. Here, animals were found to be susceptible to serially passaged serum and GBV-B transcripts. Hepatic pathology and peripheral viraemia could be quantified biochemically, immunophenotypically and morphologically, and persisted for periods of up to 6 months in some animals. Hepatitis was characterized by a marked influx of CD3+ CD8+ T lymphocytes and CD20+ B cells within the first 2 months of primary infection. The results of this study document the marmoset as another small, non-human primate species in which the pathogenesis of GBV-B can be studied and used as a surrogate model of HCV infection for investigation of pathogenesis and antiviral drug development.

scholarly journals Epigenetic clock and DNA methylation studies of roe deer in the wild

2020 ◽  
Author(s):  
Jean-François Lemaître ◽  
Benjamin Rey ◽  
Jean-Michel Gaillard ◽  
Corinne Régis ◽  
Emmanuelle Gilot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Evolutionary Biology ◽  
Roe Deer ◽  
Chronological Age ◽  
Epigenetic Clock ◽  
Aging Effects ◽  
Methylation Array ◽  
Biomarkers Of Aging ◽  
Epigenetic Age ◽  
The Relationship

AbstractDNA methylation-based biomarkers of aging (epigenetic clocks) promise to lead to new insights in the evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic aging effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois Fontaines, France) facing different ecological contexts to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n=90 blood samples using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age through the use of sex-specific epigenetic clocks. Our results highlight that both populations and sex influence the epigenetic age, with the bias toward a stronger male average age acceleration (i.e. differences between epigenetic age and chronological ages) particularly pronounced in the population facing harsh environmental conditions. Further, we identify the main sites of epigenetic alteration that have distinct aging patterns across the two sexes. These findings open the door to promising avenues of research at the crossroad of evolutionary biology and biogerontology.

scholarly journals Electrical microstimulation evokes saccades in posterior parietal cortex of common marmosets

2019 ◽  
Vol 122 (4) ◽  
pp. 1765-1776 ◽  
Author(s):  
Maryam Ghahremani ◽  
Kevin D. Johnston ◽  
Liya Ma ◽  
Lauren K. Hayrynen ◽  
Stefan Everling
Keyword(s):  
Eye Movements ◽  
Parietal Cortex ◽  
Posterior Parietal Cortex ◽  
Common Marmoset ◽  
Primate Species ◽  
Oculomotor Control ◽  
Electrical Microstimulation ◽  
Cortical Areas ◽  
Posterior Parietal ◽  
The Common

The common marmoset ( Callithrix jacchus) is a small-bodied New World primate increasing in prominence as a model animal for neuroscience research. The lissencephalic cortex of this primate species provides substantial advantages for the application of electrophysiological techniques such as high-density and laminar recordings, which have the capacity to advance our understanding of local and laminar cortical circuits and their roles in cognitive and motor functions. This is particularly the case with respect to the oculomotor system, as critical cortical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) lie deep within sulci in macaques. Studies of cytoarchitecture and connectivity have established putative homologies between cortical oculomotor fields in marmoset and macaque, but physiological investigations of these areas, particularly in awake marmosets, have yet to be carried out. Here we addressed this gap by probing the function of posterior parietal cortex of the common marmoset with electrical microstimulation. We implanted two animals with 32-channel Utah arrays at the location of the putative area LIP and applied microstimulation while they viewed a video display and made untrained eye movements. Similar to previous studies in macaques, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks. These data demonstrate that area LIP of the marmoset plays a role in the regulation of eye movements, provide additional evidence that this area is homologous with that of the macaque, and further establish the marmoset as a valuable model for neurophysiological investigations of oculomotor and cognitive control. NEW & NOTEWORTHY The macaque monkey has been the preeminent model for investigations of oculomotor control, but studies of cortical areas are limited, as many of these areas are buried within sulci in this species. Here we applied electrical microstimulation to the putative area LIP of the lissencephalic cortex of awake marmosets. Similar to the macaque, microstimulation evoked contralateral saccades from this area, supporting the marmoset as a valuable model for studies of oculomotor control.

scholarly journals Establishment of a diabetes mellitus type 1 model in the common marmoset

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wenji Yuan ◽  
Satsuki Fukuda ◽  
Takashi Inoue ◽  
Hitoshi Okochi ◽  
Erika Sasaki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Common Marmoset ◽  
Histological Evaluation ◽  
Insulin Administration ◽  
Partial Pancreatectomy ◽  
Common Marmosets ◽  
Diabetes Model ◽  
The Common

Abstract Common marmosets have attracted considerable attention as a small standard primate model in biomedical research. However, no marmoset diabetes model is available. Here, we established a marmoset diabetes model via the combination of partial pancreatectomy and intravenous streptozotocin (STZ). A partial pancreatectomy was performed in 11 common marmosets and multiple STZ doses were intravenously administered. Diabetes was diagnosed upon sustained hyperglycaemia (nonfasting blood glucose level >200 mg/dl). Blood glucose and biochemistry were periodically assessed, in addition to glucose tolerance testing, continual blood glucose determination using a continuous glucose monitoring system, urine testing and histological evaluation. In 8 of the 11 animals (73%), diabetes mellitus was induced. The diabetic marmosets also showed abnormal intravenous and oral glucose tolerance test results. Blood glucose levels decreased in response to human insulin administration. The hyperglycaemic state was irreversible and persisted for more than 3 months, and the animals’ condition was manageable via daily insulin administration. Thus, diabetes can be successfully induced and maintained in the common marmoset via partial pancreatectomy and STZ administration. This protocol effectively generates a valuable animal model for studying disease pathogenesis, risk factors and therapeutic interventions, including islet transplantation.

scholarly journals Expression of taste signal transduction molecules in the caecum of common marmosets

2013 ◽  
Vol 9 (4) ◽  
pp. 20130409 ◽  
Author(s):  
Sae Gonda ◽  
Shuichi Matsumura ◽  
Shoichiro Saito ◽  
Yasuhiro Go ◽  
Hiroo Imai
Keyword(s):  
Signal Transduction ◽  
Immunohistochemical Analysis ◽  
Common Marmoset ◽  
Rt Pcr ◽  
Common Marmosets ◽  
Plant Exudates ◽  
The Common ◽  
Signal Transduction Proteins ◽  
First Time ◽  
Human Primate

The extraoral presence of taste signal transduction proteins has recently been reported in rodents and humans. Here, we report for the first time the presence of these signal transduction proteins in the caecum of a non-human primate, the common marmoset. Quantitative RT-PCR data on the gene expression of taste signal transduction molecules (gustducin and TRPM5) in common marmosets suggested high expression in the caecum, which was not observed in other non-human primates. Immunohistochemical analysis confirmed the specific presence of gustducin and taste receptors in marmoset caecal cells. These results may relate to the specific feeding behaviour of marmosets, which consume plant exudates, primarily gums.

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